Preventative strategies for low anterior resection syndrome.

BACKGROUND: A common and debilitating complication of low anterior resection for rectal cancer is low anterior resection syndrome (LARS). As a multifactorial entity, LARS is poorly understood and challenging to treat. Despite this, prevention strategies are commonly overlooked. Our aim was to review the pathophysiology of LARS and explore current evidence on the efficacy and feasibility of prophylactic techniques. METHODS: A literature review was performed between [1st January 2000 to 1st October 2023] for studies which investigated preventative interventions for LARS. Mechanisms by which LARS develop are described, followed by a review of prophylactic strategies to prevent LARS. Medline, Cochrane, and PubMed databases were searched, 189 articles screened, 8 duplicates removed and 18 studies reviewed. RESULTS: Colonic dysmotility, anal sphincter dysfunction and neorectal dysfunction all contribute to the development of LARS, with the complex mechanism of defecation interrupted by surgery. Transanal irrigation (TAI) and pelvic floor rehabilitation (PFR) have shown benefits in preventing LARS, but may be limited by patient compliance. Intraoperative nerve monitoring (IONM) and robotic-assisted surgery have shown some promise in surgically preventing LARS. Nerve stimulation and other novel strategies currently used in treatment of LARS have yet to be investigated in their roles prophylactically. CONCLUSIONS: To date, there is a limited evidence base for all preventative strategies including IONM, RAS, PFP and TAI. These strategies are limited by either access (IONM, RAS and PFP) or acceptability (PFP and TAI), which are both key to the success of any intervention. The results of ongoing trials will serve to assess acceptability, while technological advancement may improve access to some of the aforementioned strategies.

Clinical response to antibiotic regimens in lower limb cellulitis: a systematic review.

There is variation in the treatment of lower limb cellulitis (LLC) with no agreement on the most effective antibiotic regimen. Many patients with cellulitis fail to respond to first-line antibiotics. This can negatively affect patient care and result in unnecessary hospital admissions. The aim of this systematic review was to determine the clinical response and safety of antibiotic regimens for the management of LLC. A systematic review for randomized controlled trials (RCTs) was conducted using OVID MEDLINE, Ovid Embase and Cochrane Central Register of Controlled Trials in January 2019. Outcomes of interest included the clinical response to antibiotic regimens (type, dose, route, duration) and the safety of antibiotics in LLC. Trial quality was identified using the Cochrane Risk of Bias tool. Four RCTs were included. All included studies showed no significant differences between the clinical response to different antibiotic type, administration route, treatment duration or dose. LLC may be overtreated and shorter courses of oral antibiotics, possibly with lower doses, may be more suitable. There is a lack of published data on the clinical response and safety of antibiotics in LLC. Three studies were high risk for bias overall. Further high-quality studies may help determine whether less intensive antibiotic regimens can effectively treat LLC.

Patients' understanding of cellulitis and views about how best to prevent recurrent episodes: mixed-methods study in primary and secondary care.

BACKGROUND: Cellulitis is a common painful infection of the skin and underlying tissues that recurs in approximately one-third of cases. The only proven strategy to reduce the risk of recurrence is long-term, low-dose antibiotics. Given current concerns about antibiotic resistance and the pressure to reduce antibiotic prescribing, other prevention strategies are needed. OBJECTIVES: To explore patients' views about cellulitis and different ways of preventing recurrent episodes. METHODS: Adults aged ≥ 18 years with a history of first-episode or recurrent cellulitis were invited through primary care, hospitals and advertising to complete a survey, take part in an interview or both. RESULTS: Thirty interviews were conducted between August 2016 and July 2017. Two hundred and forty surveys were completed (response rate 17%). Triangulation of quantitative and qualitative data showed that people who have had cellulitis have wide-ranging beliefs about what can cause cellulitis and are often unaware of risk of recurrence or potential strategies to prevent recurrence. Enhanced foot hygiene, applying emollients daily, exercise and losing weight were more popular potential strategies than the use of compression stockings or long-term antibiotics. Participants expressed caution about long-term oral antibiotics, particularly those who had experienced only one episode of cellulitis. CONCLUSIONS: People who have had cellulitis are keen to know about possible ways to prevent further episodes. Enhanced foot hygiene, applying emollients daily, exercise and losing weight were generally viewed to be more acceptable, feasible strategies than compression or antibiotics, but further research is needed to explore uptake and effectiveness in practice.

A systematic review showing the lack of diagnostic criteria and tools developed for lower-limb cellulitis.

BACKGROUND: Cellulitis can be a difficult diagnosis to make. Furthermore, 31% of patients admitted from the emergency department with suspected lower-limb cellulitis have been misdiagnosed, with incorrect treatment potentially resulting in avoidable hospital admission and the prescription of unnecessary antibiotics. OBJECTIVES: We sought to identify diagnostic criteria or tools that have been developed for lower-limb cellulitis. METHODS: We conducted a systematic review using Ovid MEDLINE and Embase databases in May 2018, with the aim of describing diagnostic criteria and tools developed for lower-limb cellulitis, and we assessed the quality of the studies identified using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We included all types of study that described diagnostic criteria or tools. RESULTS: Eight observational studies were included. Five studies examined biochemical markers, two studies assessed imaging and one study developed a diagnostic decision model. All eight studies were considered to have a high risk for bias in at least one domain. The quantity and quality of available data was low and results could not be pooled owing to the heterogeneity of the findings. CONCLUSIONS: There is a lack of high-quality publications describing criteria or tools for diagnosing lower-limb cellulitis. Future studies using prospective designs, validated in both primary and secondary care settings, are needed. What's already known about this topic? Diagnosing lower-limb cellulitis on first presentation is challenging. Approximately one in three patients admitted from the emergency department with suspected lower-limb cellulitis do not have cellulitis and are given another diagnosis on discharge. Consequently, this results in potentially avoidable hospital admissions and the prescription of unnecessary antibiotics. There are no diagnostic criteria available for lower-limb cellulitis in the U.K. What does this study add? This systematic review has identified a key research gap in the diagnosis of lower-limb cellulitis. There is a current lack of robustly developed and validated diagnostic criteria or tools for use in clinical practice.

Neoadjuvant chemoradiation for rectal cancer is not associated with higher rates of thromboembolism.

AIM: Thromboembolism (TE) is a leading cause of death amongst cancer patients. The effect of neoadjuvant chemoradiotherapy (nCRT) on the risk of TE in rectal cancer patients is unknown. The aim of this study was to determine whether nCRT was associated with an increased risk of TE in patients with rectal cancer, either during therapy or with subsequent treatment. METHOD: This was a retrospective study from a prospectively maintained database at a tertiary referral centre. Participants included patients with rectal cancer treated between January 2000 and December 2013. The primary outcome was the rate of TE in patients with rectal cancer who had nCRT compared with those who did not. RESULTS: One hundred and seventy-one (7.8%) of 2181 rectal cancer patients developed TE. Patients who had nCRT did not have an increased incidence of TE compared with those who had surgery alone (81/946, 8.6% vs 94/1235, 7.6%, P = 0.42) after a median follow-up of 95 months. Ten (1.1%) of 946 patients who received nCRT developed TE during or immediately after nCRT. Most TE events occurred in the 30-day postoperative period (70 patients, 3.2%). CONCLUSION: The prevalence of TE in patients with rectal cancer was 7.8%, with most events occurring in within 30 days of surgery. Neoadjuvant chemoradiation was not associated with an increased risk of TE.

Thromboembolism during neoadjuvant therapy for rectal cancer: a systematic review.

AIM: Thromboembolism (TE) is a common, costly and morbid complication that is also associated with decreased survival in cancer patients. However, the risk of cancer-associated TE varies because of the multitude of patient-, cancer- and treatment-related influences. Thromboprophylaxis (TP) is currently not widely adopted in the ambulant population. A review of the literature was undertaken to determine the rate of TE and the benefit of TP in patients with rectal cancer during neoadjuvant therapy (nT). METHOD: A systematic literature search of electronic databases, including PubMed and Embase, was performed (1995-2012) for all studies assessing nT in rectal cancer. Data were extracted and used to assess study design, patient demographic and clinical characteristics, treatment protocols and TE incidence. A systematic review was conducted to identify the rates of TE. The search strategy included text terms and MeSH headings for TP, rectal cancer and nT. RESULTS: Twelve of 86 studies met quality criteria for reporting TE complications and described 10 pulmonary emboli and three deep-vein thromboses in 3375 patients (overall TE rate = 0.38%). Ninety per cent of pulmonary emboli reported were fatal, suggesting significant under-reporting of TE events, even in high-quality studies. CONCLUSION: The risk of fatal pulmonary embolism in studies examining nT in rectal cancer that reported complications systematically was one in 375 (0.27%; 95% CI: 0.09-0.44%). The overall TE rate, as well as the effectiveness of TP during nT, remains unknown. TE events should be systematically reported using common terminology frameworks in cancer studies.

Robotic-assisted complete mesocolic excision, central vascular ligation and para-aortic lymph node dissection in multifocal carcinoid: A case report and technical description.

INTRODUCTION: Neuroendocrine tumours are the most common type of primary small bowel neoplasm. Consensus guidelines recommend a multimodal approach to treatment of such tumours, with aggressive surgical resection remaining the mainstay of management. There is evidence that complete mesocolic excision (CME) of lymph nodes is associated with superior oncological outcomes including longer disease-free survival in patients with colorectal cancer than standard lymph node dissection and there is increasing evidence to suggest that the robotic approach may be superior to laparoscopic or open CME. This report discusses a robotic-assisted approach to CME with central vessel ligation (CVL) and para-aortic lymph node dissection in a case of multifocal neuroendocrine tumour of the small bowel. PRESENTATION OF CASE AND TECHNICAL APPROACH: This report details the case of a 73-year-old male with multifocal small bowel neuroendocrine tumour. He underwent a robotic-assisted right hemicolectomy, small bowel resection, CME, CVL and para-aortic lymph node dissection. The approach described involved undertaking CME, CVL and bowel resection with a standard right hemicolectomy robotic set-up before re-docking the robot to perform the retroperitoneal para-aortic lymph node dissection. DISCUSSION: This case highlights the management of multifocal small bowel neuroendocrine tumour using a robotic approach for surgical resection and lymph node clearance. CONCLUSION: The robotic approach provides a safe and effective technique for undertaking surgical resection of small bowel neuroendocrine tumour as well as complete mesocolic excision of lymph nodes. With a change in port positions, a robotic approach can be utilised for CME/CVL as well as retroperitoneal node dissection.

Robotic complete mesocolic excision using indocyanine fluorescence imaging in colorectal cancer: A case study and technical approach.

INTRODUCTION: Colorectal cancer is the second most common malignancy in developed countries and accurate staging is vital for determining the most appropriate management plan, in particular, whether adjuvant chemotherapy is recommended in addition to surgical resection. There is currently no consensus regarding standard practice for lymph node resection in colorectal cancer although there is increasing evidence to support the use of sentinel lymph node mapping to target lymph node sampling and facilitate ultra-staging of nodes. PRESENTATION OF CASE: We present the case of a 49 year old female who underwent a robotic right hemicolectomy and complete mesocolic excision for caecal adenocarcinoma using indocyanine fluorescence imaging (ICG FI) to guide nodal dissection. DISCUSSION: ICG FI may be useful for sentinel lymph node mapping in colorectal cancer. This technique can assist to identify the first draining lymph nodes and permit ultra-staging of lymph nodes. CONCLUSION: While there is still limited evidence to support ICG FI, the current body of literature suggests that it is likely to be a feasible and sensitive technique for guiding sentinel lymph node sampling in colorectal cancer.

Extremely large variations of atmospheric 14C concentration during the last glacial period.

A long record of atmospheric 14C concentration, from 45 to 11 thousand years ago (ka), was obtained from a stalagmite with thermal-ionization mass-spectrometric 230Th and accelerator mass-spectrometric 14C measurements. This record reveals highly elevated Delta14C between 45 and 33 ka, portions of which may correlate with peaks in cosmogenic 36Cl and 10Be isotopes observed in polar ice cores. Superimposed on this broad peak of Delta14C are several rapid excursions, the largest of which occurs between 44.3 and 43.3 ka. Between 26 and 11 ka, atmospheric Delta14C decreased from approximately 700 to approximately 100 per mil, modulated by numerous minor excursions. Carbon cycle models suggest that the major features of this record cannot be produced with solar or terrestrial magnetic field modulation alone but also require substantial fluctuations in the carbon cycle.

Effects on normal fibroblasts and neuroblastoma cells of the activation of the p53 response by the nuclear export inhibitor leptomycin B.

p53 tumour suppressor protein levels and p53-dependent transcriptional activity have been recently shown to increase in cells treated with leptomycin B (LMB), an inhibitor of nuclear export. Experiments presented here show that LMB treatment leads to growth arrest and a senescence-like phenotype in human normal fibroblast cultures. This effect is reversible after removal of the drug and further passage by trypsinization. Instead, LMB has a strong cytotoxic effect on human neuroblastoma cell lines even at nanomolar concentrations. In both these cell types the effects of LMB are attenuated when the activity of the endogenous wild type p53 protein is abrogated by overexpression of a dominant negative p53 mutant. We conclude that the induction of the p53 response by LMB plays an important role in the effects of this drug on cultured cells.

Changes in the structural organization of chromatin during spermatogenesis in the rat.

In this study, histone H4 was shown to be extensively hyperacetylated in mid-spermatids of the rat during the time period when the entire complement of histones is replaced by basic spermatidal transition proteins. The degree of hyperacetylation of histone H4 was minimal in pachytene spermatocytes. Therefore, the hyperacetylation appears to be directly involved in the histone replacement process late in spermatogenesis in mid-spermatids. In order to investigate further the possible effects of histone H4 hyperacetylation and the other dramatic changes in the nuclear proteins on the structure of chromatin in germinal cells, we examined the thermal denaturation profiles of chromatin from various purified germinal cell types. Our analyses revealed that chromatins from pachytene spermatocytes and early spermatids have similar thermal denaturation profiles, with their major thermal transitions slightly lower than those for rat liver. However, the major thermal transitions for chromatin from mid-spermatids are much lower than those from pachytene spermatocytes and early-spermatids. We propose that the greatly lowered thermal stability of mid-spermatid chromatin represents a dramatic relaxation or decondensation of the chromatin in this cell type in preparation for the replacement of histone by the basic spermatidal transition proteins and that the decondensation is due in large part to the extensive histones hyperacetylation which occurs in these cells.

Revegetation of peat excavations in a derelict raised bog.

Thorne Waste, S. Yorkshire, is a large raised bog, subject to extensive commercial peat extraction, which retains some re-flooded, revegetated peat cuttings. The composition of the vegetation of some of these cuttings (96 sampled quadrats, each of 25 m2 ) has been related to a number of environmental variables. Revegetation sequences in the abandoned cuttings (all less than 60 years old and with less than 20 cm peat infill) were established by stratigraphical analyses. In some cuttings a basal layer of ericaceous peat apparently marks temporarily drier conditions preceding deeper inundation. Some former mire species (e.g. Sphagnum imbricatum have not survived the peat-cutting period even on uncut surfaces (baulks) but these have been much drained and burnt. The revegetated cuttings contained species typical of poor-ten (e.g. Carex curta) as well as of ombrotrophic mires (e.g. Andromeda polifolia); chemical analyses indicated weakly minerotrophic peat water. This may favour such species as Sphagnum recurvum. There was no indication of chemical enrichment from inflow from surrounding farmland, from underlying mineral ground or from the clay-lined canals excavated across the bog. Release of cations following drainage and re-flooding may provide some explanation. Only soluble reactive phosphorus (SRP) concentration in peat water samples showed consistent and significant seasonal variation, with the lowest values in summer. There were also only a few consistent differences in water chemistry amongst most of the vegetation units identified by TWINSPAN. Nodum 4 (Eriophorum-Sphagnum) stands (richest in ombrotrophic species) occupied the least minerotrophic conditions. One culling, dominated by Juncus, effuses, had no ombrotrophic species (nodum 6). Water concentrations of Ca2+ , Na+ , K+ NH4 + , SO4 2 and SRP were significantly larger here than in other cuttings and peat fertility (estimated phytometrically) and K, N and P concentrations in peat extracts were significantly greater than in a Sphagnum-dominated cutting. The J. effuses samples had strong negative loadings on axis 2 of a Principal Components Analysis (PCA) of the Adriatic data; concentrations of NH4 + , Na+ and SO4 2 in the water showed significant negative correlation with axis 2 ordination scores. Seasonal fluctuation of water level was similar in most cuttings (the J. effuses cutting was exceptional) but variation in depth relative to the peat surface (caused by excavation to different depths) was related to floristic variation. PCA axis 1 may reflect a water-table gradient with TWINSPAN noda 2 (Calluna Sphagnum recurvum) and particularly 1 (Pteridium Campylopus) occupying drier conditions than the others. The wetter cuttings (except the J. effusus site) supported most ombrotrophic and poor-fen species. They were not readily segregated into discrete vegetation types and the two TWINSPAN classes (noda 3 and 4) that accommodated them showed much overlap on the PCA ordination. Nodum 4 samples tended to have higher loadings on PCA axis 2 and to be more species-rich than nodum 3 samples. Species-richness was strongly positively correlated with PCA axis 2. This may reflect, in part, stand maturity, vegetation with most species having been disturbed least recently.

PLANTS AND PEAT CUTTINGS: HISTORICAL ECOLOGY OF A MUCH EXPLOITED PEATLAND - THORNE WASTE, YORKSHIRE, UK.

Although many lowland raised bogs have been much modified or completely destroyed by agricultural reclamation, peat cutting, unaccompanied by reclamation, is not necessarily so destructive, and abandoned workings may provide a range of habitats that can support some of the original wetland plant species. Thome Waste, a much exploited raised bog in Eastern England, has a varied and well-documented management history and comparatively good botanical records. It thus provides an exemplary site to assess the effect of peat exploitation upon its flora. The origin and development, and subsequent drainage, reclamation and peat extraction history of the site are described, and their impact upon the past and present flora is evaluated. Some ombrotrophic mire species have been lost from the site, but one section of peat cuttings (the Dutch canal system, abandoned about 1920) has revegetated and supports an important range of these plants. Fen species, which once occupied the marginal lagg, have been almost completely eliminated from their original sites (which have mostly been reclaimed) but many have become re-established in various new habitats created within the peat-cutting complex. This illustrates the potential of artificial modification of worked-over peatland sites to sustain a range of wetland plants.